Interaction between birth characteristics and CRHR1, MC2R, NR3C1, GLCCI1 variants in the childhood lymphoblastic leukemia risk

BackgroundThe incidence rate of childhood acute lymphoblastic leukemia (ALL) differs worldwide, and the interplay between hemostasis actors and the maladaptive responses to environmental exposures has been explored. It has been proposed that endogenous cortisol, induced by different triggers, would eliminate pre-leukemic clones originated in utero. Herein, we tested if the interaction between CRHR1rs242941 C>A, MC2Rrs1893219 A>G, NR3C1rs41423247 G>C, and GLCCI1rs37972 C>T (players in glucocorticoid secretion) and birth characteristics would be associated with ALL risk.MethodsChildren aged G was negatively associated with ALL (AG: OR = 0.68; 95% CI = 0.50–0.94 and GG: OR = 0.60; 95% CI = 0.42–0.85), while for GLCCI1 rs37972 C>T, TT was positively associated with ALL (OR = 1.91; 95% CI = 1.21–3.00). The combination of genotypes for MC2R (AA) and GLCCI1 (TT) increased ALL risk (OR = 2.61; 95% CI = 1.16–5.87). In a multiplicative interaction, MC2R rs1893219 A>G was associated with children whose mothers had less than 9 years of schooling (iOR = 1.99; 95% CI = 1.11–1.55).ConclusionOur study has demonstrated a significant association between MC2R rs1893219 A>G (reduced risk) and GLCCI1 rs37972 C>T variants (increased risk) and childhood ALL susceptibility. Based on this evidence, genes controlling the HPA axis activity may play a role in leukemogenesis, and further investigation is needed to substantiate our findings.